Epigenetic modifications as therapeutic targets in atherosclerosis: a focus on DNA methylation and non-coding RNAs

Abstract

Significant progress in the diagnosis and treatment of cardiovascular disease (CVD) has been made in the past decade, yet it remains a leading cause of morbidity and mortality globally, claiming an estimated 17.9 million deaths per year. Although encompassing any condition that affects the circulatory system, including thrombotic blockage, stenosis, aneurysms, blood clots and arteriosclerosis (general hardening of the arteries), the most prevalent underlying hallmark of CVD is atherosclerosis; the plaque-associated arterial thickening. Further, distinct CVD conditions have overlapping dysregulated molecular and cellular characteristics which underlie their development and progression, suggesting some common aetiology. The identification of heritable genetic mutations associated with the development of atherosclerotic vascular disease (AVD), in particular resulting from Genome Wide Association Studies (GWAS) studies has significantly improved the ability to identify individuals at risk. However, it is increasingly recognised that environmentally-acquired, epigenetic changes are key factors associated with atherosclerosis development. Increasing evidence suggests that these epigenetic changes, most notably DNA methylation and the misexpression of non-coding, microRNAs (miRNAs) are potentially both predictive and causal in AVD development. This, together with their reversible nature, makes them both useful biomarkers for disease and attractive therapeutic targets potentially to reverse AVD progression. We consider here the association of aberrant DNA methylation and dysregulated miRNA expression with the aetiology and progression of atherosclerosis, and the potential development of novel cell-based strategies to target these epigenetic changes therapeutically.

The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

“…Several of such alterations have been implicated in diseases or conditions relevant to menopause, such as osteoporosis and calcium signaling [83][84][85], cardiovascular disease [86,87], osteoarthritis [88][89][90], the nervous system and the brain [91][92][93][94], obesity [95,96], and vascular inflammation [97]. BB.…”

Epigenetics of hypertension as a risk factor for the development of coronary artery disease in type 2 diabetes mellitus

“…The methylation of DNA serves a dual purpose: it contributes to the preservation of genome integrity and exerts regulatory control over gene expression at the mRNA level ( 28 ). A multitude of studies have underscored the impact of DNA methylation on diverse pathophysiological processes, including EH, prompting extensive investigations into its role in hypertension and related cardiovascular disorders ( 29 , 30 ). For a comprehensive overview of reported epigenetic modifications, such as DNA methylation, during the course of EH, please refer to Table 1 .…”

Novel Insights into the Molecular Mechanisms of Atherosclerosis

“…DNA and miRNA methylation are important epigenetic factors in AS. This study reviews recent insights into the role of miRNA and DNA methylation and their interaction in AS progression [164]. DNA methylation in mammals appears at the fifth position of cytosine (5mC) in CpG dinucleotide and participates in transcriptional repression and cellular regulation.…”